A variety of pancreas isografts have ameliorated chemically-induced diabetes in animals. Long-term survival of any form of pancreas allograft across major histocompatibility complex differences has proven difficult to obtain in any species and under any immunosuppressive cover. Particularly, isolated pancreatic islets of Langerhans are prone to early rejection. We have developed animal models in which spleen allografts in inbred rats and inbred guinea pigs survive spontaneously and confer a donor-specific unresponsiveness to subsequent duct-ligated pancreas allografts that would otherwise be rejected. We propose the use of these rather unique animal models in a purely comparative study of morphology and function of whole-organ, duct-ligated pancreas allografts and isolated islet allografts without trying to identify the underlying immunologic mechanisms. The data obtained in omnivorous rats and herbivorous guinea pigs will further a better understanding of the strains imposed by an allogeneic environment on the functional capabilities of two distinctly different beta cell grafts under identical genetic and immunosuppressive conditions. It is ultimately hoped that this study will indicate whether or not either of the tested grafts should be given clinical preference in the surgical treatment of diabetes.